Enzymes belonging to the halohydrin dehalogenase (HHDH), also named halohydrin hydrogen-halide-lyase or halohydrin epoxidase, class (EC 4.5.1) catalyze the interconversion of 1,2-halohydrins and the corresponding 1,2-epoxides as shown below in Scheme 1.

U.S. Pat. No. 4,284,723 describes the use of a halohydrin epoxidase for the production of propylene oxide. U.S. Pat. Nos. 5,166,061 and 5,210,031 describe the use of this enzyme activity for the conversion of 1,3-dichloropropanol (DCP) and epichlorohydrin (ECH) respectively to 4-chloro-3-hydroxybutyronitrile (CHBN). HHDH enzymes from Agrobacterium radiobacter and Corynebacterium have been characterized on a broad range of halogenated substrates (Van Hylckama Vlieg et al., J. Bacteriol. (2001) 183:5058-5066; Nakamura et al., Appl. Environ. Microbiol. (1994) 60:1297-1301; Nagasawa et al., Appl. Microbiol. Biotechnol. (1992) 36:478-482).
HHDH also catalyzes the ring opening of epoxides with nucleophiles other than chloride or bromide as shown in Scheme 2 (see e.g., Nakamura et al., Biochem. Biophys Res. Comm. (1991) 180:124-130; Nakamura et al., Tetrahedron (1994) 50: 11821-11826; Lutje Spelberg et al., Org. Lett. (2001) 3:41-43; Lutje Spelberg et al., Tetrahedron Asymm. (2002) 13:1083).

Nakamura et al. (Tetrahedron (1994) 50: 11821-11826) describe the use of HHDH for the direct conversion of DCP to chloro-3-hydroxy-butyronitrile (CHBN) through epichlorohydrin (ECH) as the intermediate as shown below in Scheme 3.

Some halohydrin dehalogenases have been characterized. For example, HHDH from A. radiobacter AD1 is a homotetramer of 28 kD subunits. Corynebacterium sp. N-1074 produces two HHDH enzymes, one of which, enzyme Ia, is composed of 28 kD subunits, while the other, enzyme Ib. is composed of related subunits of 35 and/or 32 kD. HHDH from some sources is easily inactivated under oxidizing conditions in a process that leads to dissociation of the subunits, has a pH optimum from pH 8 to 9 and an optimal temperature of 50° C. (Tang, Enz. Microbial Technol. (2002) 30:251-258; Swanson, Curr. Opin. Biotechnol. (1999) 10:365-369). The optimal pH for HHDH catalyzed epoxide formation has been reported as 8.0 to 9.0 and the optimal temperature in the range of from 45° C. to 55° C. (see e.g., Van Hylckama Vlieg et al., J. Bacteriol. (2001) 183:5058-5066; Nakamura et al., Appl. Environ. Microbiol. (1994) 60:1297-1301; Nagasawa et al., Appl. Microbiol. Biotechnol. (1992) 36:478-482). The optimal pH for the reverse reaction, ring opening by chloride, has been reported for the two Corynebacterium sp. N-1074 enzymes Ia and Ib and is pH 7.4 and pH 5, respectively. Site directed mutagenesis studies on the A. radiobacter AD1 HHDH indicated that oxidative inactivation is due to disruption of the quaternary structure of the enzyme by oxidation of cysteine residues (Tang et al., Enz. Microbial Technol. (2002) 30:251-258).
Purified HHDH enzymes from different sources exhibit specific activities on DCP ranging from 146 U/mg (Ib) to 2.75 U/mg (Ia) (Nakamura et al., Appl. Environ. Microbiol. 1994 60:1297-1301; Nagasawa et al., Appl. Microbiol. Biotechnol. (1992) 36:478-482). The high activity of the Ib enzyme is accompanied by a high enantioselectivity to produce R-ECH from DCP, while the Ia enzyme produces racemic ECH.
HHDH encoding genes have been identified in Agrobacterium radiobacter AD1 (hheC), Agrobacterium tumefaciens (halB), Corynebacterium sp (hheA encoding Ia and hheB encoding Ib), Arthrobacter sp. (hheAAD2), and Mycobacterium sp. GP1 (hheBGp1). All enzymes have been functionally expressed in E. coli. 
It is highly desirable for commercial applications that an HHDH enzyme exhibits high volumetric productivity, that reactions run to completion in a relatively short period of time, with a high final product concentration, with high enantioselectivity and regioselectivity, exhibits minimal inhibition by reaction components, and that generation of undesirable chemical side products is reduced. It is also desirable to have an HHDH enzyme capable of catalyzing ring opening or ring closure on a range of substrates (Hasnaoui-Dijoux et al., 2008, Chem. Biochem. 9:1048-1051; Tang et al., 2003, Biochemistry 42:5378-5386; Lutje Spelberg et al., 2000, Org. Lett. 3(1):41-43; Lutje Spelberg et al., 1998, Tetrahedron Asymmetry 9:459-466; and Majeric-Elenkov et al., Organic Letters 10 (12), pg 2417-2420, 2008).